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p(HGNC:CASP6)

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Entity

Name
CASP6
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 2

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Inflammasome activation and innate immunity in Alzheimer’s disease v1.0.2

In-Edges 3

bp(GO:"apoptotic process") increases act(p(HGNC:CASP6)) View Subject | View Object

There may be reciprocity with the apoptosis pathway as activating caspase-3 by inducing apoptosis in cortical neuronal culture led to tau cleavage (22), and selectively expressing tauC3 led to apoptosis in NT2 and COS cells (21). This might represent a feed-forward loop of neurotoxicity. PubMed:24027553

Appears in Networks:
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Text Location
Review

path(MESH:"Alzheimer Disease") positiveCorrelation act(p(HGNC:CASP6)) View Subject | View Object

In order for caspase to cleave tau in the AD brain, it needs to be present in its active form. The active forms of both caspase-3 and caspase-6 are elevated in AD-specific brain regions (temporal and frontal lobes) compared to unaffected regions (cerebellum) and control brains (57, 58). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Temporal Lobe
Text Location
Review

act(complex(GO:"NLRP1 inflammasome complex")) increases act(p(HGNC:CASP6)) View Subject | View Object

Recently, Kaushal et al. described the involvement of NLRP1 inflammasome activation in neurons. In these experiments, serum deprivation induced NLRP1-dependent caspase-1 activity and ASC speck formation, which resulted in caspase-6 activation and an increase in the Ab42/total Ab ratio (11) PubMed:28019679

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph

Out-Edges 7

act(p(HGNC:CASP6)) increases p(HGNC:MAPT, frag("?_*")) View Subject | View Object

There is significant evidence that tau is a caspase substrate and that caspase-mediated tau cleavage may play a role in AD pathology. Early in vitro studies demonstrated that tau is cleaved in the C-terminus by several caspases including caspase-3 and caspase-6 (21–23). PubMed:24027553

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act(p(HGNC:CASP6)) increases p(HGNC:MAPT, frag("?_*")) View Subject | View Object

Furthermore, active caspase co-localizes to NFTs (58), and caspase-cleaved tau is found in AD-affected brain regions, particularly in neurons displaying tangle pathology (59, 60). This includes tau cleaved by caspase-6 in the C-terminus (58–60) as well as in the N-terminus (24). TauC3 is present in AD brain – in neurons and co-localized with NFTs – and inversely correlates with cognitive function (55, 60, 61). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

act(p(HGNC:CASP6)) increases p(HGNC:MAPT, frag("1_?")) View Subject | View Object

Caspase-6 was also shown to cleave the N-terminus of tau in vitro (24). Caspase-3, which is a key effector in the apoptotic cascade, cleaves tau predominantly at the C-terminal D421 site generating a fragment often referred to as tauC3 (22, 23). PubMed:24027553

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Text Location
Review

act(p(HGNC:CASP6)) increases p(HGNC:MAPT, frag("1_?")) View Subject | View Object

Furthermore, active caspase co-localizes to NFTs (58), and caspase-cleaved tau is found in AD-affected brain regions, particularly in neurons displaying tangle pathology (59, 60). This includes tau cleaved by caspase-6 in the C-terminus (58–60) as well as in the N-terminus (24). TauC3 is present in AD brain – in neurons and co-localized with NFTs – and inversely correlates with cognitive function (55, 60, 61). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

act(p(HGNC:CASP6)) increases bp(GO:"apoptotic process") View Subject | View Object

Caspase-6 was also shown to cleave the N-terminus of tau in vitro (24). Caspase-3, which is a key effector in the apoptotic cascade, cleaves tau predominantly at the C-terminal D421 site generating a fragment often referred to as tauC3 (22, 23). PubMed:24027553

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Annotations
Text Location
Review

act(p(HGNC:CASP6)) increases p(HGNC:MAPT, var("p.D421*")) View Subject | View Object

Caspase-6 was also shown to cleave the N-terminus of tau in vitro (24). Caspase-3, which is a key effector in the apoptotic cascade, cleaves tau predominantly at the C-terminal D421 site generating a fragment often referred to as tauC3 (22, 23). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(p(HGNC:CASP6)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

In order for caspase to cleave tau in the AD brain, it needs to be present in its active form. The active forms of both caspase-3 and caspase-6 are elevated in AD-specific brain regions (temporal and frontal lobes) compared to unaffected regions (cerebellum) and control brains (57, 58). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Frontal Lobe
MeSH
Temporal Lobe
Text Location
Review

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.